Investigating PI3P Binding with Plasmodium Falciparum HSP70 Proteins

Abstract

Background: Plasmodium falciparum (P. falciparum) heat shock proteins (PfHSP70s) are an important class of molecules critically involved in parasite survival during stress. Interaction between the cytosolic PfHSP70-1 and a crucial lipid modulator, Phosphatidylinositol 3 Phosphate (PI3P), stabilizes the parasite Digestive Vacuole (DV) to facilitate hemoglobin trafficking and breakdown, in turn impacting parasite survival. Methods: PI3P binding on PfHSP70-1 is facilitated by its C-terminal LID domain that controls substrate binding. PI3P and PfHSP70 homologs are amply expressed together in various subcellular compartments of the parasite, providing them with opportunities to interact and modulate biological processes. Results: Here, we have identified and analyzed the PI3P binding pockets of all four PfHSP70s by using structural bioinformatics tools to understand their interaction with this lipid. Our results show that differently localized PfHSP70 homologs bind PI3P with variable affinity. Conclusion: Analysis of these results has also helped to pinpoint specific residues on PfHSP70s that may be engaged in these interactions. The present study may, therefore, form the basis for designing interventions that hinder PfHSP70-PI3P interaction and influence parasite survival.